АР09259390 «Study of the effect of SARS-CoV-2 coronavirus antigens on the pro-inflammatory activity of neutrophils, monocytes and T-regulatory cells». Academic Supervisor – PhD Ostapchuk Y.O.

General conception of the project

            The COVID-19 pandemic has led to an unprecedented health crisis worldwide. A better understanding of the immune response to SARS-CoV-2 will be critical for the application and development of therapeutics. The data available to date indicate a high risk of mortality from COVID-19 in the elderly population, as well as the leading role of neutrophils, monocytes and dysregulation of the immune response in the development of severe disease and poor prognosis. The present study is aimed at studying the immune response of neutrophils, monocytes and the population of immunoregulatory T-lymphocytes of healthy young and elderly people to the SARS-Cov-2 protein antigens in vitro to uncover the mechanisms of immunopathogenesis and the causes of severe COVID-19.

 

The goal of the project is to study the immune response of monocytes, neutrophils and T-regulatory cells of young healthy donors and the elderly to SARS-CoV-2 antigens.

Tasks of the project:

1) To study the immune response of monocytes isolated from the peripheral blood of young healthy donors and the elderly to SARS-Cov-2 antigens.

Explanation: Assessment of the pro-inflammatory activity of monocytes obtained from the peripheral blood of young donors and elderly people, who are at risk for the severity of the course and mortality from COVID-19, upon contact with SARS-Cov-2 antigens ex vivo, will help to uncover the mechanisms of immunopathogenesis and identify predictors the severity of the course of COVID-19. The pro-inflammatory activity of monocytes will be studied by analyzing the level of expression of molecular activation markers, pathogen-recognizing receptors, major histocompatibility complex type II (HLA-II) molecules, transcription factors, and the production of pro-inflammatory cytokines. Commercially available coronavirus proteins S, N and M will be used as SARS-Cov-2 antigens. Healthy people aged 18 to 40 and elderly people over 65 years old will be selected as peripheral blood donors.

“Check-point” result: indicators of the pro-inflammatory activity of monocytes obtained from the peripheral blood of young healthy donors and the elderly in response to exposure to SARS-Cov-2 antigens ex vivo.

2) To study the immune response of neutrophils isolated from the peripheral blood of young healthy donors and the elderly to SARS-Cov-2 antigens.

Explanation: Evaluation of the pro-inflammatory activity of neutrophils obtained from the peripheral blood of young donors and the elderly, upon contact with SARS-Cov-2 antigens in vitro, will facilitate unraveling of the mechanisms of immunopathogenesis of COVID-19, which causes hyperinflammation and damage to lung tissue and other organs. The level of pro-inflammatory activity of neutrophils will be studied by analyzing the expression of molecular markers of activation, pathogenic receptors, chemokine receptors, as well as the production of reactive oxygen species.

“Check-point” result: indicators of pro-inflammatory activity of neutrophils obtained from the peripheral blood of young healthy donors and elderly people in response to exposure to SARS-Cov-2 antigens in vitro.

3) To study the immunosuppressive activity of T-regulatory cells (Treg) isolated from the peripheral blood of young healthy donors and the elderly in response to exposure to SARS-Cov-2 antigens.

Explanation: Treg cells are involved in maintaining immune homeostasis, suppressing the activity of both innate and adaptive immunity. Disruption of the functional activity of Treg cells can cause dysregulation of the immune response and contribute to the development of a hyperinflammatory response in COVID-19. Study of the immunosuppressive activity of Treg cells obtained from the peripheral blood of young donors and the elderly in a comparative aspect, including the expression of immunosuppression markers, the FoxP3 transcription factor associated with the immunosuppressive activity of Treg cells, the expression and production of anti-inflammatory cytokines, as well as the immunosuppressive activity against autologous T-lymphocytes in response to SARS-Cov-2 antigens in vitro will also contribute to the unraveling of the mechanisms of immunopathogenesis of COVID-19.

 “Check-point” result: indicators of immunosuppressive activity of Treg cells obtained from the peripheral blood of young healthy donors and elderly people in response to exposure to SARS-Cov-2 antigens in vitro.

Project implementation in 2021 and obtained results:

Task # 1.1 “Study the response of monocytes isolated from the peripheral blood of young healthy donors to SARS-Cov-2 antigens”

Obtained results:

Pro-inflammatory activity of monocytes isolated from the peripheral blood of donors aged 18 to 40 years in response to the recombinant antigens S1 and N of the SARS-Cov-2 virus was analyzed by the level of molecular activation markers, pathogen-recognizing receptors, HLA-II antigens expression and the production of pro-inflammatory cytokines.

 

Task # 1.2 “Study the response of monocytes isolated from the peripheral blood of the elderly to SARS-Cov-2 antigens”.

Obtained results:

Pro-inflammatory activity of monocytes isolated from the peripheral blood of elderly donors over 65 years in response to the recombinant antigens S1 and N of the SARS-Cov-2 virus was analyzed by the level of molecular activation markers, pathogen-recognizing receptors, HLA-II antigens expression and the production of pro-inflammatory cytokines. A comparative analysis of the obtained data between the two groups of donors was carried out. 

Publication and implementation of results:

Кан С.А., Остапчук Е.О. Нарушение активности некоторых субпопуляций Т-клеток при тяжелом течении COVID-19. Актуальные проблемы теоретической и клинической медицины. – 2021. – Т. 31, №1. –С. 36-40.

 

Research team:

  1. Ostapchuk .O., D (biology), project leader, leading researcher. Hirsch index: 5. In total – 20 publications, 100 citations. ORCID: http://orcid.org/0000-0002-3771-423X. Scopus ID: 56823472400. WoS ID: D-1254-2015.
  2. Perfileva Y.V., D (biology), responsible executor, leading researcher. Hirsch index: 5. In total – 19 publications, 85 citations. ORCID: http://orcid.org/0000-0001-6803-0773. Scopus ID: 56823500600. WoS ID: AAF-9666-2020.
  3. Tleuliyeva R., Ph.D. (biology), head of laboratory. Hirsch index: 5. In total – 13 publications, 48 citations. ORCID: http://orcid.org/0000-0001-8897-9986. Scopus ID: 6507202148. WoS ID: N-5634-2017.
  4. Abdolla N., D. (biology), senior researcher. ORCID: http://orcid.org/0000-0002-4769-7824. Scopus ID: 57194001982. WoS ID: R-2193-2016.
  5. Kali А., MS, senior researcher. ORCID: http://orcid.org/0000-0002-5129-1165. Scopus ID: 57195580717. WoS ID: AAF-9781-2020.
  6. Kan S.А., MS student, junior researcher.
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